SMC1A

structural maintenance of chromosomes 1A, the group of MicroRNA protein coding host genes|Cohesin complex|Structural maintenance of chromosomes proteins

Basic information

Region (hg38): X:53374148-53422728

Previous symbols: [ "SMC1L1" ]

Links

ENSG00000072501 ∙ NCBI:8243 ∙ OMIM:300040 ∙ HGNC:11111 ∙ Uniprot:Q14683 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cornelia de Lange syndrome 2 (Definitive), mode of inheritance: XLD
• Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
• atypical Rett syndrome (Supportive), mode of inheritance: AD
• Cornelia de Lange syndrome 2 (Definitive), mode of inheritance: XL
• developmental and epileptic encephalopathy, 85, with or without midline brain defects (Strong), mode of inheritance: XL
• Cornelia de Lange syndrome 2 (Strong), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cornelia de Lange syndrome 2; Developmental and epileptic encephalopathy 85, with or without midline brain defects	XL	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	16604071; 20358602; 20635401; 26386245; 26752331; 31334757

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMC1A gene.

• Congenital muscular hypertrophy-cerebral syndrome (620 variants)
• not provided (170 variants)
• Inborn genetic diseases (52 variants)
• not specified (28 variants)
• Congenital muscular hypertrophy-cerebral syndrome;Developmental and epileptic encephalopathy, 85, with or without midline brain defects (17 variants)
• Developmental and epileptic encephalopathy, 85, with or without midline brain defects;Congenital muscular hypertrophy-cerebral syndrome (17 variants)
• Developmental and epileptic encephalopathy, 85, with or without midline brain defects (15 variants)
• De Lange syndrome (13 variants)
• SMC1A-related condition (5 variants)
• SMC1A-related cohesinopathy (2 variants)
• History of neurodevelopmental disorder (2 variants)
• Epileptic encephalopathy (1 variants)
• Cornelia de Lange syndrome 1;Developmental and epileptic encephalopathy, 85, with or without midline brain defects (1 variants)
• Abnormal facial shape;Global developmental delay (1 variants)
• Microcephaly (1 variants)
• See cases (1 variants)
• 6 conditions (1 variants)
• Abnormality of the nervous system (1 variants)
• Intellectual disability (1 variants)
• 8 conditions (1 variants)
• Cornelia de Lange syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMC1A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	163	7	173
missense	16	45	163	12	4	240
nonsense	19	5				24
start loss						0
frameshift	37	7				44
inframe indel	1	6	8			15
splice donor/acceptor (+/-2bp)	4	6	1			11
splice region		2	19	27	3	51
non coding		1	61	80	41	183
Total	77	70	236	255	52

Variants in SMC1A

This is a list of pathogenic ClinVar variants found in the SMC1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-53374157-G-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53374188-A-G		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53374248-C-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53374250-T-C		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53374381-T-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53374411-C-T		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53374597-T-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53374614-C-A		Congenital muscular hypertrophy-cerebral syndrome	Conflicting classifications of pathogenicity (Jan 01, 2023)
X-53374622-C-T		Congenital muscular hypertrophy-cerebral syndrome	Benign (Jan 12, 2018)
X-53374652-T-C		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53374659-C-T		Congenital muscular hypertrophy-cerebral syndrome	Benign (Jan 12, 2018)
X-53374660-G-C		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53374723-C-T		De Lange syndrome	Likely benign (Jun 14, 2016)
X-53374748-C-T		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53374751-G-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53374852-C-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53374906-A-G		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53375052-C-A		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53375087-A-G		Congenital muscular hypertrophy-cerebral syndrome	Benign (Jan 12, 2018)
X-53375105-A-G		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)
X-53375149-GGT-G		De Lange syndrome	Likely benign (Jun 14, 2016)
X-53375216-A-G		Congenital muscular hypertrophy-cerebral syndrome	Benign (Jan 12, 2018)
X-53375458-A-G		De Lange syndrome	Likely benign (Jun 14, 2016)
X-53375522-A-G		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 12, 2018)
X-53375660-C-T		Congenital muscular hypertrophy-cerebral syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMC1A	protein_coding	protein_coding	ENST00000322213	25	48608

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.77e-8	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	6.45	100	510	0.196	0.0000431	8229
Missense in Polyphen		14	210.32	0.066566		3237
Synonymous	0.190	171	174	0.982	0.0000127	2196
Loss of Function	6.43	0	48.1	0.00	0.00000372	831

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint. {ECO:0000269|PubMed:11877377}.
• Disease: DISEASE: Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:16604071, ECO:0000269|PubMed:17221863, ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:18996922, ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:20358602, ECO:0000269|PubMed:20635401, ECO:0000269|PubMed:24124034}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Cell Cycle;miRNA Regulation of DNA Damage Response;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;Retinoblastoma (RB) in Cancer;Constitutive Androstane Receptor Pathway;Nuclear Receptors Meta-Pathway;Pathways Affected in Adenoid Cystic Carcinoma;ATM Signaling Network in Development and Disease;Liver steatosis AOP;mRNA Processing;Regulation of sister chromatid separation at the metaphase-anaphase transition;DNA Damage Response;Signal Transduction;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Reproduction;SUMOylation;Establishment of Sister Chromatid Cohesion;S Phase;Meiotic synapsis;Meiosis;Signaling by Nuclear Receptors;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Estrogen-dependent gene expression;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;ESR-mediated signaling;ATM pathway (Consensus)

Recessive Scores

• pRec: 0.251

Intolerance Scores

• loftool: 0.0219
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.958
• hipred: Y
• hipred_score: 0.840
• ghis: 0.559

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Smc1a
• Phenotype: immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: smc1a
• Affected structure: neural tube
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: mitotic sister chromatid segregation;DNA repair;sister chromatid cohesion;mitotic sister chromatid cohesion;response to radiation;stem cell population maintenance;negative regulation of DNA endoreduplication;cell division;meiotic cell cycle;response to DNA damage checkpoint signaling;regulation of mitotic spindle assembly
• Cellular component: chromosome, centromeric region;kinetochore;condensed chromosome kinetochore;condensed nuclear chromosome;nucleus;nucleoplasm;chromosome;cytosol;cohesin complex;nuclear matrix;meiotic cohesin complex;mitotic spindle pole
• Molecular function: chromatin binding;RNA binding;protein binding;ATP binding;mediator complex binding;protein heterodimerization activity